This invention relates in general to Time-of-Flight Mass Spectrometers and relates more particularly to special structures for increasing the resolution of such mass spectrometers.
In the figures, the first digit of a reference numeral indicates the first figure in which is presented the element indicated by that reference numeral.
In a typical time-of-flight spectrometer, a sample is ionized by a short pulse of localized energy to produce an initial region of ions that is localized both spatially and temporally. These ions are accelerated by an electric potential and are usually allowed to drift through at least one field-free region before they reach a detector that detects the reception of these ions. Within these field-free regions, the ion trajectories within this beam are substantially parallel so that the beam does not become unduly large when it reaches the next element within the spectrometer.
The electric field accelerates each ion to a velocity proportional to the square root of the ratio of the ion charge to the ion mass so that the time of arrival at the detector is inversely proportional to the square root of the mass of each ion. Therefore, a timer is started at the time of the energy pulse and the measured interval until a given group of ions reaches the detector is utilized to identify the charge to mass ratio of these ions. A mass spectrum of the sample is generated from the intensity of detected ions as a function of time. A time-of-flight spectrometer provides the significant advantages that a complete mass spectrum is produced by each pulse, that many mass spectra can be produced per second and that there is no limit on the mass range.
The initial velocity of an ion affects its time-of-flight. In the discussions which follow, the ion optical elements have cylindrical symmetry about the direction of the ion acceleration and drift. This direction will be referred to herein as the "longitudinal direction". The direction perpendicular to the direction of ion acceleration will be referred to as the "lateral direction". Likewise, the components of an ion's initial velocity will be referred to herein as the "longitudinal component of the initial velocity" and the "lateral component of the initial velocity".
It is well known (see, for example, the article R. Frey, et al A High-Resolution Time-of-Flight Mass Spectrometer Using Laser Resonance Ionization, Z. Naturforsch., Teil A, (1985) Vol. 40, pp, 1349-1350) that the resolution of mass peaks is increased by reducing as much as possible the initial spatial and temporal dimensions of the spacetime region in which ions are generated and by countering peak broadening due to kinetic energy differences of the ions at the time of generation. If ions are generated over a significant time interval, then the measured time of flight will not be equal to the actual time of flight for each ion. It is therefore important to minimize the temporal spread of ion generation. If the spatial spread of ion generation is significant, then these ions will have unequal spatial paths. More significantly, since the ions are generated in an accelerating electric field, if they are generated over a significant spatial interval along the direction of this electric field, then the ions will receive a significant spread of energies. Because identical ions accelerated to different energies will have different time-of-flight values, such energy spreads will degrade the resolution of the time-of-flight spectrum.
An ion reflector is utilized to compensate for the part of the time-of-flight differences that arises from initial differences in the longitudinal component of the drift velocity. For ions of equal charge-to-mass ratio, those ions with a larger initial positive longitudinal component would arrive at the detector earlier than ions with zero longitudinal component. At the ion reflector, the higher energy ions penetrate farther into the reflector, thereby spending a greater time in the reflector than those with zero initial longitudinal component. The reflector parameters are selected so that the differential times spent in the ion reflector compensate for the time-of-flight differences resulting from the longitudinal velocity component differences of the ions.
In the article by Frey, et al, a gridless ion reflector is presented to avoid the perturbations introduced by an ion reflector utilizing conductive grids. A laser pulse is used to ionize a gaseous sample because a laser has the extremely small spatial and temporal width needed to produce high resolution. Also, the laser can be tuned to enable selective ionization of one sample component and the wavelength of the laser can be selected to produce ions either with or without fragmentation of the initial particles.
In addition to the use of a reflector to compensate for initial potential energy differences of ions, other techniques are available to prevent initial kinetic and potential energy differences from degrading resolution. As taught in the article M. Yang, et al, A Reflectron Mass Spectrometer With UV Laser-Induced Surface Ionization, International Journal of Mass Spectrometry and Ion Processes, 75 (1987) 209-219, the initial potential energy spread is substantially eliminated by adsorbing sample molecules onto the surface of a prism and then directing the laser beam through the prism onto these adsorbed sample molecules. This surface is perpendicular to the electric acceleration field so that all of these particles have the same initial potential energy. To avoid ionizing gas molecules above the surface, the laser beam is directed to internally reflect off of the metallized surface on which the particles are adsorbed.
Other factors identified in this article as affecting resolution include: the flatness of electric grids; and the stability and accuracy of the delay time generator. This latter problem is addressed in the following patent issued to Yvon Le Beyec, et al.
U.S. Pat. No. 4,694,168 entitled Time-of-Flight Mass Spectrometry issued to Yvon Le Beyec et al on Sep. 15, 1987 is directed to the accurate detection of neutral and ionized fragments from particles that decay during flight in the spectrometer. Sample ions are produced by bombardment with a high energy primary ion from a 2-particle decay process. A time-of-flight timer is started in response to detection of the 2nd of these 2 decay particles, thereby providing accurate activation of this counter.
The article X. Tang, et al, A Secondary Ion Time-of-Flight Mass Spectrometer With An Ion Mirror, International Journal of Mass Spectrometry, (1988) pp. 42-66 provides a detailed analysis of operation and errors of this system. Daughter ions have substantially the same velocity as the parent, and therefore are equivalent to parent ions in the ion spectrum. However, the lower energy of daughters means that they spend a shorter time in the mirror, thereby separating them from the parent particles in the spectrum. This separation improves sensitivity compared to systems without an ion mirror. To enable determination of decay rates, a movable target enables the distance from the ion source to the reflector to be varied. An adjustable iris preserves the angular acceptance angle as this distance is varied. A long flight path is utilized for improved resolution and a short path is utilized for higher efficiency, which is useful in the low intensity correlation measurements.
Because of the above-listed advantages of secondary ion time-of-flight mass spectrometers, it is desirable to extend the application of such mass spectrometers to the high mass ions encountered in medical and biological applications. Fortunately, the article R. J. Beuhler and L. Friedman, Threshold Studies Of Secondary Electron Emission Induced By Macro-Ion Impact On Solid Surfaces, Nuclear Instruments and Methods, 170 (1980), p. 309-315 teaches that the actual rate of secondary electron emission is much greater for high mass secondary ions than is predicted by the classical analysis which treats the incident primary ion as a single particle having an ability to scatter high mass secondary ions according to the classical principles of conservation of energy and momentum. Instead, to explain the much higher than expected rate of generation of secondary electrons by very high mass ions, this article concludes that the incident ion must be treated as a collection of its component layers of atoms, each of which can separately contribute energy to the secondary electron formation process. Because of this, time-of-flight mass spectrometry for typical biological molecules is feasible in spite of their very high mass.
In the article Georges Slodzian, Microanalyzers Using Secondary Ion Emission in the text Applied Charged Particle Optics, edited by A. Septier, Academic Press, 1980, the ion optics section utilizes an immersion lens followed by an einzel lens.
In the article J. Orloff and L. W. Swanson, An Asymmetric Electrostatic Lens For Field-emission Microprobe Applications, J. Appl. Phys. 50(4), April 1979, p. 2494, an asymmetric lens is analyzed for use as the accelerating element in high current (tens of nanoamperes) electron beams for submicron beams. This type of lens has the advantage of providing continuous voltage variability of focus while maintaining a fixed image and object distance.